Formulation and Evaluation of Cetirizine Hydrochloride Fast-Disintegrating Tablets using Chitosan and Stevia Leaf Powder

Priyanka R. Ahire¹*, Pradnya M. Khandagale², Manisha M. Rokade³

¹Lecturer, Department of Pharmaceutics,

KCT’S R G Sapkal Institute of Pharmacy, Anjaneri, Nashik, 422213 Maharashtra India.

²Lecturer, Department of Quality Assurance,

KCT’S R G Sapkal Institute of Pharmacy, Anjaneri, Nashik 422213 Maharashtra India.

³HOD Department of Pharmaceutics,

KCT’S R G Sapkal Institute of Pharmacy, Anjaneri, Nashik 422213 Maharashtra India.

*Corresponding Author E-mail: priyankapatil88605@gmail.com, pradnyamkhandagale@gmail.com, rokademanisha3131@gmail.com

ABSTRACT:

The present study focuses on the formulation and evaluation of Cetirizine dihydrochloride fast-disintegrating tablets using chitosan and natural sweetener Stevia leaf powder to enhance patient compliance in allergic conditions. Fast-disintegrating tablets dissolve in the mouth without the need for water, thereby improving bioavailability by facilitating pre-gastric absorption. Chitosan, a natural polymer derived from chitin, was used as a disintegrant due to its biocompatibility, biodegradability, and swelling properties, while Stevia provided taste masking. Five formulations (F1–F5) were prepared by direct compression using mannitol, microcrystalline cellulose, and other excipients. The formulations were evaluated for flow properties, thickness, hardness, friability, wetting time, water absorption ratio, disintegration time, drug content uniformity, in-vitro dissolution, and accelerated stability. The results demonstrated uniformity in tablet parameters, satisfactory mechanical strength, rapid disintegration, improved taste, and near-complete drug release within 6 minutes. Formulations F4 and F5 showed optimal stability over a 3-month period under accelerated conditions. The study confirms that chitosan and Stevia can be successfully used in fast-disintegrating tablets to enhance patient compliance and drug efficacy.

KEYWORDS: Cetirizine Hydrochloride, Chitosan, Stevia leaf Powder, Fast Disintgating Tablet.

INTRODUCTION:

A fast-disintegrating tablet dissolves in the mouth without water in less than 1 minute, leaving a pleasant sensation^1,2. When a tablet is placed in the mouth, saliva readily dissolves it. Tablets may be dissolved in the mouth with just a tiny amount of saliva, eliminating the need for water³. Orally disintegrating pills are a useful option for juvenile, geriatric, mentally ill, recalcitrant, and traveling patients without rapid access to water⁴. Tablets of this type can be used to improve bioavailability of poorly soluble substances. Some of the drug is absorbed in the mouth, pharynx, and esophagus as the saliva passes down into the stomach; the bioavailability of the drug is significantly greater than those observed in conventional tablet dosage forms⁵. Any pre-gastric absorption avoids first pass hepatic metabolism and increases the bioavailability of the           drug ².

To achieve faster disintegration, the tablet manufacturers use disintegrants, which break the tablet matrix into smaller fragments in the presence of saliva^1,6–8. The disin tegrants can be synthetic and natural. Advantages of natural substances over synthetic are numerous: local availability from a renewable source, low cost, biodegradable, and eco-friendly^6,8,9.

One example is medium molecular weight chitosan. Chitosan is a linear binary heteropolysaccharide composed of 1,4-linked glucosamine with varying degrees of N-deacetylation, which is generated by deacetylating chitin. Crab and shrimp shells, as well as mushroom cell walls, naturally contain chitin¹⁰. Chitosan's solubility, viscosity, coagulation, and heavy metal ion chelation depend on its molecular weight and degree of deacetylation¹¹. Chitosan is a cationic polysaccharide that exhibits antioxidant, antibacterial, lipid-lowering, film-forming, and gelling activities¹². It has many roles in pharmaceutical formulations, including binder in wet granulation, diluent in direct compression, tablet disintegrant, and permeation enhancer. Hydrogels made from N-trimethyl chitosan with high or medium molecular weight were highly effective. Chitosan hydrogels have excellent water-holding capacity, rheological properties, and strong adhesion to the mucosal membrane. The sol-gel transition happened within 7 minutes at 32.5°C¹¹. Deacetylation of chitin, a slow biodegrading and weakly soluble material, results in a more soluble polymer ideal for quick dissolving tablets¹³.

Cetirizine dihydrochloride (CET) is a second-generation antihistaminic drug indicated for the treatment of allergies. CET is an extremely bitter drug requiring effective taste-masking; therefore it was chosen as a model drug. The purpose of the present study was to design Cetirizine hydrochloride mouth dissolving tablets using chitosan, natural sweetener Stevia (Stevia rebidiana) leaf powders, to achieve patient compliance in allergic disorder^14-16.

Materials:

Cetirizine hydrochloride was a gift sample from Cipla, Mumbai, India. Stevia leaf powder was obtained from the Vedas oil, India. Mannitol, talc, micro crystalline cellulose, Cross carmellose sodium, magnesium stearate and talc were purchased from S.D. Fine Chemicals, Mumbai, India. All other chemicals, solvents and reagents were used of either pharmacopoeial or analytical grade.

Flow Properties of the Blend:^17-18

Angle of Repose:

Funnel method was adopted to determine the Angle of repose. The blend was poured through a funnel that can be raised vertically until a maximum cone height (h) was obtained. Radius of the heap (r) was measured and the angle of repose was calculated. It is the angle produced between the heap of the pile and base. The Angle of repose can be mathematically calculated by the following equation.

tan (θ) = h / r

Where, θ = Angle of repose,

h = Height of heap and r = Radius of pile.

Loose Bulk Density:

It was determined by pouring the blend into a graduated cylinder. The bulk volume (V) and weight of the powder (M) b was determined. Mathematically loose bulk density can be calculated by the following equation.

LBD = M / V_b

Where, M = Weight of powder and V_b= Bulk volume

Tapped Bulk Density:

Measuring cylinder method was adopted for this. A known quantity of formulation blend was taken in a graduated measuring cylinder and tapped for a fixed time. The minimum volume (V) occupied in the cylinder and the weight (M) of the t blend was measured. Mathematically tapped bulk density can be calculated by the following equation.

TBD = M / V_t

Where, M = Weight of powder and V = Volume after tapping t

Compressibility Index:

It is an easiest way of measuring flow ability of powders. The loose and tapped bulk density values were considered in calculating compressibility index. Mathematically it can be calculated by the following equation.

I = [(V_b – V_t) / V_b] x 100

Where, V_b = Bulk volume and V_t = Tapped volume

Hausner Ratio:

Hausner ratio is an indirect index of ease of powder flow. It is the ratio of TBD to LBD. Mathematically loose bulk density can be expressed and calculated by the following equation.

Hausner ratio = TBD / LBD

Where, TBD = Tapped bulk density and LBD = Loose bulk density

Method:

All the ingredients were passed through sieve # 60. Cetirizine hydrochloride, mannitol, Micro Crystalline Cellulose and Stevia leaf powder were triturated in a glass mortar. Micro crystalline cellulose, Cross carmellose sodium, chitosan were incorporated in the powder mixture and finally magnesium stearate and talc were added. The mixed blend was then compressed with 10mm flat face surface punches using hydraulic press single tablet punching machine. As per Table no. 1

Formulation Batches^19-20

Table 1 formulation Batches

Ingredients (mg)	Formulation
	F1	F2	F3	F4	F5
Cetirizine Hydrochloride	10	10	10	10	10
Microcrystaline Cellulose	214	212	210	208	206
Mannitol	50	50	50	50	50
Chitosan	10	12	14	16	18
Cross carmelose sodium	5	5	5	5	5
Magnesium stearate	3	3	3	3	3
Talc	3	3	3	3	3
Stevia leaf powder	5	5	5	5	5

Evaluation of Post compression parameters: ^21-29

Thickness:

The thickness of the tablets was determined using a thickness screw gauge (ISC Technologies, Kochi, India). Three tablets from each batch were used and average values were calculated.

Hardness test:

The hardness of the formulated tablets was determined using Monsanto hardness tester (Cadmach, Ahmedabad, India). It is expressed in kg/cm². Three tablets were randomly picked and analyzed for hardness. The mean and standard deviation values were also calculated.

Friability Test:

The friability of tablets was determined using Roche Friabilator (Campbell Electronics, Mumbai, India). The friabilator was operated at 25 rpm for 4 min (totally 100 revolutions). The % friability was then calculated by the following equation.

F= W_initial – W_final / W_initial X 100

Where, F= friability (%),

W_initial= initial weight and w_final= final weight

Weight Variation test:

Twenty tablets of each formulation were weighed using an electronic balance (Denver APX-100, Arvada, Colorado) and the test was conducted as per the official procedure.

Drug Content Uniformity:

Tablet containing 10mg of drug is dissolved in 100ml of 0.1N HCl taken in volumetric flask. The drug is allowed to dissolve and the solution was filtered, 1ml of filtrate was taken in 50ml of volumetric flask and diluted with 0.1N HCl and analyzed spectrophotometrically (Elico SL 210, India) at 233nm. The concentration of Cetirizine hydrochloride mg/ml was obtained by using standard calibration curve of Cetirizine hydrochloride. Drug content studies were carried out in triplicate for each formulation batch.

Wetting Time:

The tablet was placed in a petridish of 6.5cm in diameter, containing 10ml of water at room temperature, and the time for complete wetting was recorded. To check for reproducibility, the measurements were carried out six times and the mean value calculated.

Water Absorption Ratio:

A small piece of tissue paper folded twice and placed in a petri dish containing 6ml of distilled water. A tablet was kept on the paper and time taken by the tablet for complete wetting was measured. The wetted tablet was then weighed. Water absorption ratio, R, was determined using the following equation.

R = 10 X (Wa – Wb) / Wb

Where, Wb = weight of the tablet before water absorption

Wa = weight of the tablet after water absorption

Three tablets from each formulation were analysed performed and standard deviation was also determined.

In-vitro Dispersion Time:

Tablet was placed in 10ml phosphate buffer solution, pH 0 6.8±0.5C. Time required for complete dispersion of a tablet was measured.

In-vitro Disintegration Time:

The in vitro disintegration time of tablets were performed by placing one tablet in each of the 6 tubes of the basket. Add a disc to each tube and run the apparatus using pH 6.8 0 (simulated saliva fluid) maintained at 37±2C as the immersion liquid. The assembly should be raised and lowered between 30 cycles per min in the pH 6.8 maintained 0 at 37±2C. The time taken for the complete disintegration of the tablet with no palpable mass remaining in the basket was measured and recorded.

In-vivo Disintegration Time:

Six healthy human volunteers (both sexes) were selected, each volunteer was allowed to one tablet and kept on the tongue. The time taken by the tablet (in seconds) for complete disintegration on the surface of the tongue was noted. After the test, mouth was washed with distilled water. Three trials were performed with 2 days interval, between trials.

Accelerated Stability Studies:

The promising formulations (F-4 and F-5) was tested stability for a period of 3 months at accelerated storage conditions of a 0 temperature 40C and a relative humidity of 75% RH, for their 16-drug content

Table 2 The physicochemical properties of powdered blend

Formulation	Angle of Rpose (ø)	Loose Bulk Density (g/cm3)	Tapped Bulk Density (g/cm3)	Carr’s Index (%)	Hauser’s Ratio
F-1	29.32±0.81	0.57±0.077	0.68±0.023	16.18±0.05	1.192±0.01
F-2	28.98±0.48	0.55±0.052	0.71±0.051	22.50±0.02	1.291±0.04
F-3	28.73±0.86	0.59±0.066	0.69±0.065	14.56±0.02	1.169±0.01
F-4	27.20±1.57	0.57±0.032	0.65±0.083	12.35±0.06	1.141±0.03
F-5	26.30±0.15	0.58±0.075	0.66±0.094	12.12±0.10	1.143±0.02
Number of trials(n)=3

Results of Flow Properties:

The formulated blend was evaluated for various parameters such as angle of repose, loose bulk density, tapped bulk density, compressibility index and Hausner ratio. The values were within the official limits with less standard deviation. The results of angle of repose was ranged from 26.300.15 to 0 29.320.81 indicate good flow properties. Loose bulk density 3 of the blends was ranged from 0.550.052 to 0.590.066g/cm and tapped bulk density was ranged from 0.650.083 to 3 0.710.051 g/cm. The LBD and TBD values were considered in calculating compressibility index, which was ranged from 12.12±0.10 to 22.50±0.02% and Hausner ratio ranged from 1.141±0.03 to 1.291±0.04. These values indicate that the formulated powder blend shows satisfactory flow property. All these values were represented in Table No. 2.

Results of Physicochemical Properties of Tablets:

The mean thickness of formulated tablets was found to be uniform (2.980.15 to 3.050.02mm), the hardness of 3 formulated tablets was more than 5kg/cm (5.940.26 to 3 7.95±0.19kg/cm) and the loss in friability was less than 1% (0.26±0.08 to 0.56±0.09%) indicated the formulated tablets have good mechanical strength. All the tablets passed weight variation test as per the pharmacopoeial limits. The Wetting Time (928.95 to 1005.66 s) indicates that all the formulated tablets has quick wetting, this may be due to ability of swelling and also capacity of absorption of water. The water absorption ratio (12.51±0.02 to 16.59±0.15g) favors the wetting of the tablet in saliva. The disintegration time (228.26 to 392.32 s) was within the pharmacopoeial limits aided with the presence of cross cormilose sodium and chitosan, in direct compression method results in hydrophilicity and swelling which in turn causes rapid disintegration. The volunteers felt good taste in all the formulations. As the formulation was not bitter due to the presence of stevia leaf powder, which is 400 times sweeter than sucrose. In oral disintegration all the formulations showed rapid disintegration in oral cavity. All these values were represented in Table No 3. In all the formulations the drug release was nearer to 100% within 6 min. This rapid dissolution might be due to fast breakdown of particles of superdisintegrants. The parameters in all the formulations the drug release was nearer to 100% within 6 min. This rapid dissolution might be due to fast breakdown of particles of superdisintegrants. The parameters in In-vitro dissolution studies were shown in Table No. 4. The In-vitro dissolution profile of formulated tablets was shown in Figure 1. The optimized formulations F-4 and F-5 were subjected to accelerated stability studies and the tablets possessed the same parameters even after the stressed conditions, indicates good stability properties of formulation. The comparative parameters of optimized formulations (F-4 and F-5) before and after the accelerated stability studies were shown in Table 5.

Table 3: Evaluation parameters of Tablets

Formulation	Thickness (mm)	Hardness (kg/cm3)	Friability (5)	Wetting time(s)	Water absorption ratio	Disintegration time(s)	Mouth feel
F-1	3.0±20.08	6.38±0.13	0.35±0.01	100±5.66	12.51±0.02	35±4.25	Good
F-2	3.0±30.05	6.10±0.17	0.56±0.09	92±8.95	13.56±0.10	39±2.32	Good
F-3	2.9±80.15	7.95±0.19	0.29±0.09	95 ±6.66	14.25±0.14	32±6.59	Good
F-4	3.0±30.01	6.95±0.51	0.26±0.08	99±4.59	15.16±0.09	22±8.26	Good
F-5	3.0±50.02	5.94±0.26	0.54±0.05	98±3.87	16.59±0.15	31±4.61	Good

Table 4: Tablet Dissolution Apparatus Parameters

Parameter	Value
Dissolution medium	900 ml of 0.1N Hcl
Temperature	370C10C
RPM	50
Tablet taken	One tablet (Known drug content)
Volume withdrawn	5 ml every 2 min
Volume made up to	5 ml
max	233 nm
Beer's range	1-10 g/ml
Dilution factor	10

Fig. 1 In-vitro dissolution profile of formulated tablets

Table 5: Physical properties of F-4 and F-5 till 90 days when stored at 400C/75% RH

Formulation	Tested After Time (days)	Hardness (kg/cm2)	Disintegration time (s)	Wetting time (s)	Friability (%)
F-4	0	6.95±0.51	22±8.26	99±4.59	0.26±0.08
	30	6.95±0.68	21±5.62	98±6.51	0.28±0.05
	60	6.94±0.48	20±4.54	97±2.51	0.27±0.07
	90	6.94±0.26	21±5.89	98±2.64	0.28±0.03
F-5	0	5.94±0.26	31±4.61	98±3.87	0.54±0.05
	30	5.95±0.27	30±2.87	99±4.85	0.55±0.01
	60	5.91±0.24	30±3.57	97±5.98	0.58±0.04
	90	5.90±0.15	29±5.21	96±5.62	0.57±0.06

CONCLUSION:

Fast-disintegrating tablets of Cetirizine dihydrochloride were successfully formulated using chitosan as a natural disintegrant and Stevia leaf powder for taste masking. The prepared tablets exhibited good flow properties, mechanical strength, and rapid disintegration both in vitro and in vivo. The optimized formulations (F4 and F5) demonstrated excellent stability, high drug release, and improved mouth feel. The use of chitosan not only enhanced disintegration but also contributed to better bioavailability and patient acceptability. This study highlights the potential of natural excipients like chitosan and Stevia in developing effective and patient-friendly fast-disintegrating tablet formulations.

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Received on 17.09.2025      Revised on 08.11.2025

Accepted on 26.12.2025   Published on 13.04.2026

Available online from April 15, 2026

Asian J. Pharm. Tech. 2026; 16(2):138-142.

DOI: 10.52711/2231-5713.2026.00019

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